It is well known that vitamin D is essential for proper bone growth and development and for the maintenance of blood calcium levels within the normal physiological range. It is also known that this activity of vitamin D depends on the metabolic conversion of the vitamin to its biologically active metabolites. Specifically, it has been shown that 1.alpha.,25-dihydroxyvitamin D.sub.3 (1,25-(OH).sub.2 D.sub.3), the dihydroxylated metabolite normally formed from vitamin D.sub.3 in the animal or human, is the active species responsible for regulating calcium transport in the intestine, and calcium resorption from bone (bone mobilization), thereby controlling the overall blood calcium level of the organism, and assuring the maintenance of calcium homeostasis. (These calcium-related activities of vitamin D metabolites or analogs will, in the following description, be referred to collectively as the "calcemic activity" of the compounds.) The discovery of the biologically active metabolites of vitamin D has stimulated the preparation of many synthetic analogs, such as, for example, 1.alpha.-hydroxy-vitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, fluorinated vitamin D derivatives, as well as analogs with altered side chains, and some of the natural, as well as several of the synthetic compounds, because of their biological potency and beneficial effects on calcium balance, have found use, or have been proposed, as therapeutic agents in the prophylaxis or treatment of various calcium metabolism and bone disorders, such as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis and related diseases.
It has also been shown that 1,25-(OH).sub.2 D.sub.3 and certain related analogs, in addition to their "calcemic activity" as summarized above, also show potent activity in inhibiting the proliferation of malignant cells and inducing their differentiation to normal cells. (This activity will be referred to herein as the "differentiation activity" of vitamin D compounds.) Because of their remarkable potency as differentiation-inducing agents, 1.alpha.-hydroxyvitamin D compounds have been proposed as anticancer agents, at least for certain types of cancers (Suda et al. U.S. Pat. No. 4,391,802). More recently, a number of vitamin D side chain homologs have been disclosed, including, for example, the 24-homo-, 26-homo-, 26,27-dimethyl- and the 26,27-diethyl analogs of 1,25-(OH).sub.2 D.sub.3, which are reported to be preferentially active as differentiation-inducing agents [DeLuca et al. U.S. Pat. No. 4,717,721; Sai et al., Chem. Pharm. Bull. 33, 878 (1985); Ikekawa et al., Chem. Pharm. Bull. 35, 4362 (1987)]. In addition, 1.alpha.-hydroxyvitamin D compounds have been proposed for the treatment of certain skin disorders, such as psoriasis [Dikstein and Hartzshtark, U.S. Pat. No. 4,610,978]. This broad spectrum of activities and the varied potential uses of vitamin D compounds have further stimulated the search for novel analogs with desirable biological properties.